{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T07:41:46Z","timestamp":1762674106262},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2016,5,21]],"date-time":"2016-05-21T00:00:00Z","timestamp":1463788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,11,1]]},"abstract":"<jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Among the most significant developments to have taken place in osteology over the last few decades is an evolution from treating and viewing bone disorders primarily through an endocrine lens to instead seeing them as metabolic disorders that interface at the molecular and cellular level with the immune system. Osteoimmunology was officially born in response to accumulating evidence that the immune system is integrally involved in bone remodeling, but much of the early work focused on the role of conventional \u03b1\u03b2 T cells in driving bone loss. There is, however, emerging data indicating that innate lymphocytes, in particular \u03b3\u03b4 T cells, may in fact be important for bone regeneration. We first observed that bisphosphonate-associated osteonecrosis of the jaw (ONJ), a rare but serious adverse drug effect characterized by nonhealing necrotic bone tissue of the mandible or maxilla, was linked to a deficiency in a subset of \u03b3\u03b4 T cells found in human peripheral blood. Patients who developed ONJ while on bisphosphonate therapy not only lacked the main subset of circulating \u03b3\u03b4 T cells, but they also all had underlying conditions that compromised their immune integrity. A number of recent studies have unraveled the role of \u03b3\u03b4 T cells (and lymphocytes sharing their characteristics) in bone regeneration\u2014particularly for fracture healing. These findings seem to contradict the prevailing view of such \u201cinflammatory\u201d T cells as being bone degenerative rather than restorative. This viewpoint melds together the emerging evidence of these so-called inflammatory T cells in bone remodeling and healing\u2014showing that they are not in fact \u201call bad to the bone.\u201d \u00a9 2016 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.2875","type":"journal-article","created":{"date-parts":[[2016,5,23]],"date-time":"2016-05-23T20:35:12Z","timestamp":1464035712000},"page":"1997-2000","source":"Crossref","is-referenced-by-count":23,"title":["It May Seem Inflammatory, but Some T Cells Are Innately Healing to the Bone"],"prefix":"10.1093","volume":"31","author":[{"given":"Shirin","family":"Kalyan","sequence":"first","affiliation":[{"name":"CeMCORDivision of Endocrinology, Department of MedicineUniversity of British ColumbiaVancouverCanada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,5,21]]},"reference":[{"key":"2024021014170256700_jbmr2875-bib-0001","doi-asserted-by":"crossref","first-page":"1677E","DOI":"10.1096\/fj.15.10.1677e","article-title":"Bone builders: the discoveries behind preventing and treating osteoporosis","volume":"15","author":"Patlak","year":"2001","journal-title":"FASEB J"},{"key":"2024021014170256700_jbmr2875-bib-0002","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.immuni.2012.01.016","article-title":"Rank signaling links the development of invariant gammadelta T cell progenitors and Aire(+) medullary epithelium","volume":"36","author":"Roberts","year":"2012","journal-title":"Immunity"},{"key":"2024021014170256700_jbmr2875-bib-0003","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1038\/nm1518","article-title":"Epidermal RANKL controls regulatory T-cell numbers via activation of dendritic cells","volume":"12","author":"Loser","year":"2006","journal-title":"Nat Med"},{"key":"2024021014170256700_jbmr2875-bib-0004","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1146\/annurev.immunol.20.100301.064753","article-title":"RANK-L and RANK: T cells, bone loss, and mammalian evolution","volume":"20","author":"Theill","year":"2002","journal-title":"Annu Rev Immunol"},{"key":"2024021014170256700_jbmr2875-bib-0005","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/36593","article-title":"A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function","volume":"390","author":"Anderson","year":"1997","journal-title":"Nature"},{"key":"2024021014170256700_jbmr2875-bib-0006","doi-asserted-by":"crossref","first-page":"25190","DOI":"10.1074\/jbc.272.40.25190","article-title":"TRANCE is a novel ligand of the tumor necrosis factor receptor family that activates c-Jun N-terminal kinase in T cells","volume":"272","author":"Wong","year":"1997","journal-title":"J Biol Chem"},{"key":"2024021014170256700_jbmr2875-bib-0007","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/35046196","article-title":"Bone versus immune system","volume":"408","author":"Arron","year":"2000","journal-title":"Nature"},{"key":"2024021014170256700_jbmr2875-bib-0008","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1038\/46303","article-title":"Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand","volume":"402","author":"Kong","year":"1999","journal-title":"Nature"},{"key":"2024021014170256700_jbmr2875-bib-0009","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1038\/35046102","article-title":"T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-gamma","volume":"408","author":"Takayanagi","year":"2000","journal-title":"Nature"},{"key":"2024021014170256700_jbmr2875-bib-0010","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.cmet.2008.07.001","article-title":"T cells potentiate PTH-induced cortical bone loss through CD40L signaling","volume":"8","author":"Gao","year":"2008","journal-title":"Cell Metab"},{"key":"2024021014170256700_jbmr2875-bib-0011","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.cmet.2009.07.010","article-title":"T lymphocytes amplify the anabolic activity of parathyroid hormone through Wnt10b signaling","volume":"10","author":"Terauchi","year":"2009","journal-title":"Cell Metab"},{"key":"2024021014170256700_jbmr2875-bib-0012","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1073\/pnas.1013492108","article-title":"Ovariectomy disregulates osteoblast and osteoclast formation through the T-cell receptor CD40 ligand","volume":"108","author":"Li","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2024021014170256700_jbmr2875-bib-0013","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1002\/jbmr.1769","article-title":"Can peripheral blood gammadelta T cells predict osteonecrosis of the jaw? 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